Merck KGaA Oral Investigational Treatment Cladribine Tablets for

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                                                                    Phyllis Carter
News Release                                                        Phone +49 6151 72-7144


January 23, 2009


Merck KGaA: Oral Investigational Treatment Cladribine Tablets for
Multiple Sclerosis Significantly Reduced Relapse Rate in Phase III Pivotal
Trial

    •    Two-year primary efficacy endpoint of CLARITY trial met: 58% relative
         reduction in annualized relapse rate in the low total dose treatment group
         and 55% in the high total dose treatment group
    •    Submission for registration of cladribine tablets planned for mid-2009
    •    Cladribine tablets are the first oral investigational multiple sclerosis
         treatment to complete a two-year pivotal study


Darmstadt, Germany, January 23, 2009 – Merck KGaA and its Merck Serono division
announced today that the CLARITY1 Phase III pivotal trial of its proprietary oral
formulation of cladribine (cladribine tablets) met the two-year primary endpoint of
clinical relapse rate reduction in patients with relapsing-remitting multiple sclerosis
(MS).


The two cladribine tablet treatment groups of the study, assessing different dose
regimens, demonstrated a statistically significant reduction in the annualized rate of
relapses compared to placebo. Patients from the lower total dose group experienced a
58% relative reduction in annualized relapse rates with respect to placebo (0.14 versus
0.33 for the placebo group; p<0.001). Patients from the higher total dose group
experienced a 55% relative reduction in annualized relapse rates with respect to
placebo (0.15 versus 0.33; p<0.001).


Overall, the frequencies of adverse events were low in the cladribine tablet treatment
groups and were comparable to that observed in the placebo group. Lymphopenia, an

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expected event based on the presumed mechanism of action of cladribine, occurred
more frequently in the cladribine tablet treatment groups. With the exception of
lymphopenia, the most frequently reported adverse events in the three study groups
were headaches and nasopharyngitis.


“We believe the CLARITY data mark an important milestone in the assessment of
investigational oral treatments for multiple sclerosis and that cladribine tablets have the
potential to make a real difference in the lives of patients,” said Elmar Schnee,
Executive Board Member with responsibility for the Pharmaceuticals business sector.
“Based on the successful completion of the CLARITY study, we plan to submit
cladribine tablets for registration to the EMEA and to the FDA for mid-2009."


Secondary endpoints of the CLARITY study were also met, including reduction of
lesion activity as measured by magnetic resonance imaging (MRI), proportion of
subjects relapse-free and disability progression. Full study results will be submitted for
presentation at an upcoming scientific meeting.


The CLARITY study was a two-year (96 weeks), randomized, double-blind, placebo-
controlled, international trial. It enrolled 1,326 patients with relapsing-remitting MS
according to the revised McDonald criteria2. Study participants were randomized to one
of three different treatment groups consisting of two different dose regimens of
cladribine tablets or matching placebo tablets (1:1:1 ratio). Cladribine tablets were
given in two or four treatment courses in the first year, with each course consisting of
once daily administration for four to five consecutive days, which means study patients
took cladribine tablets for only 8 to 20 days during the year. In the second year, two
treatment courses were administered to all patient groups. The primary endpoint of the
CLARITY study was the qualifying relapse rate at 96 weeks. Secondary endpoints
included MRI endpoints3, proportion of subjects relapse-free and disability progression
at 96 weeks. Out of the 1,326 randomized patients, 90% of patients treated with
cladribine tablets completed the study (92% in the lower total dose group and 89% in
the higher total dose group) compared to 87% in the placebo group.




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1
  CLARITY: CLAdRIbine Tablets Treating MS OrallY
2
  The McDonald criteria are diagnostic criteria for MS. In April 2001 an international panel in association
with the National Multiple Sclerosis Society (NMSS) of America recommended revised diagnostic criteria
for MS. They make use of advances in MRI imaging techniques and are intended to replace the Poser
criteria. The new criteria facilitate the diagnosis of MS in patients who present with signs and symptoms
suggestive of the disease. The McDonald criteria for the diagnosis of multiple sclerosis were revised in
2005 to simplify and speed diagnosis, while maintaining adequate sensitivity and specificity.
3
  The exact correlation between MRI findings and the current or future clinical status of patients, including
disability progression, is unknown.


About cladribine tablets
Merck Serono’s proprietary oral formulation of cladribine (cladribine tablets) is currently being evaluated in
Phase III as a treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small
molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly
lymphocytes, which are thought to be involved in the pathological process of MS.
The clinical development program for cladribine tablets includes:
- The CLARITY (CLAdRIbine Tablets Treating MS OrallY) extension study: a two-year placebo-controlled
extension of the CLARITY study, designed to provide data on the long-term safety and efficacy of
extended administration of cladribine tablets for up to four years
- The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial
designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of
developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was
announced in September 2008.
- The ONWARD (Oral Cladribine Added ON To Rebif New Formulation in Patients With Active Relapsing
Disease) study: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability
of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced
breakthrough disease while on established interferon-beta therapy. This trial was announced in January
2007.
Cladribine tablets have been granted a fast track designation by the US Food and Drug Administration
based on the need for an oral therapy in a subset of patients with relapsing forms of multiple sclerosis.

About Merck Serono and multiple sclerosis
                                                                   ®
Merck Serono is a leader in multiple sclerosis (MS) with Rebif (interferon beta-1a), a disease-modifying
drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full
prescribing information for this product can be obtained by contacting the Company or visiting its website.
Additional therapeutic options are currently under development at Merck Serono, including cladribine
tablets, currently in Phase III and potentially the first oral therapy for MS, as well as several products in
early stage development. Merck Serono also is taking a leading role in developing an understanding of the
role of genetics in MS.

About multiple sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory condition of the nervous system and is the most
common, non-traumatic, disabling neurological disease in young adults. The World Health Organization
estimates that up to 2.5 million people suffer from MS worldwide. While symptoms can vary, the most
common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with
strength and coordination. The relapsing forms of MS are the most common.




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Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a
history that began in 1668, and a future shaped by 32,458 employees in 59 countries. Its success is
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shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was
expropriated and has been an independent company ever since.




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